• YAKHAK HOEJI
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• v.57 no.1
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• pp.18-23
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• 2013

The objective of this study is to evaluate the synergic effects of combined treatment with taurine and cisplatin in human breast cancer, MCF-7 cells. For this study, MCF-7 cells were treated with taurine (5, 10, and 20 mM) and cisplatin (0.5 ${\mu}M$) for 48 and 72 hrs. Co-treatment of cisplatin with taurine decreased cell proliferation more compared with cisplatin alone. Reduced cell proliferation was caused by apoptosis. Therefore we investigated the apoptotic cells. After treatment of cisplatin and taurine, apoptotic cells were slightly increased. Apoptosis-related proteins, cleaved caspases and cytochrome c were increased. The present study suggests that combination treatment of cisplatin with taurine enhance anticancer activity of cisplatin in MCF-7 cells.

• Natural Product Sciences
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• v.25 no.4
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• pp.311-316
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• 2019

Artocarpus heterophyllus has been used as traditional medicine. This plant is one of the sources of flavonoid. Flavonoid compounds possessed a wide range of biological properties including anticancer. This study was performed to investigate the cytotoxic effect of flavonoids from A. heterophyllus on H460 and MCF-7 cell lines. The interaction of flavonoids and cisplatin against tested cancer cells was also evaluated. MTT assay was used to determine the cytotoxic effect of flavonoid. Isobologram analysis was selected to evaluate the synergistic effect between flavonoid and cisplatin, their interaction was then confirmed using AO/PI staining method. Amongst of flavonoid compounds, artocarpin exhibited strong cytotoxic effect on both MCF-7 and H460 cell lines with IC₅₀ values of 12.53 ㎍/mL (28.73 μM) and 9.77 ㎍/mL (22.40 μM), respectively. This compound enhanced anticancer activity of cisplatin against H460 and MCF-7. The combination produced a synergistic effect on H460 and MCF-7 cell lines with a combination index (CI) values of 0.2 and 0.18, respectively. The AO/PI stained demonstrated that the combination of artocarpin and cisplatin caused morphological changes that indicated apoptosis. Moreover, artocarpanone also significantly increased cytotoxic effect of cisplatin compared to its single concentration with CI below than 1. This result suggested the potency of flavonoid named artocarpin to enhance the anticancer activity of cisplatin on H460 and MCF-7 cell lines.

• Environmental Analysis Health and Toxicology
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• v.14 no.1_2
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• pp.13-19
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• 1999

Cisplatin is an inorganic complex formed by a central atom of platinum surrounded by chlorine and ammonia atoms in the cis position in the horizontal plane, Cisplatin is one of the most effective anticancer drug, widely used against various tumor such as testicular tumor, brain tumor, ovary tumor, bladder carcinoma, colon cancer etc. However its clinical use has been limited by nephrotoxicity, ototoxicity , gastrointestinal disturbances, myeloscrppression and allergic reactions. In these toxicities, dose related and cumulative nephrotoxicity is the major dose limit factor. So, to evaluate the protective effect of aspalactone on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally, Protective effects of aspalactone against nephrotoxicity of cisplatin were observed when aspalactone was administered to rats 1hr beforecisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and aspalactone was not observed. The present results indicate that aspalactone may provide protection against cisplatin nephrotoxicity, when it is given 1hr before cisplatin injection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.992-997
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• 2007

Cisplatin is a chemotherapeutic drug which is widely used for cancer therapy including cervical cancer. The purpose of this study is to elucidate synergistic effect of Cisplatin and Berberine on the apoptosis of HeLa cells and to determine whether oxidants are formed as part of apoptotic process. Apoptotic death of HeLa cells by cisplatin and berberine was confirmed by chromatin condensation of HeLa cells and flow cytometric analysis of intracellular ROS(reactive oxygen species) production. In MTT assay, Cell viability was decreased and enhanced ROS generation in combination of cisplatin and berberine significantly, as compared with cisplatin only. Synergistic effect of Cisplatin and Berberine on the inhibition of cell growth by apoptosis was clearly observed and ROS may play an important role in apoptosis. This effect suggest the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.

• Biomedical Science Letters
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• v.14 no.2
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• pp.83-89
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• 2008

We have compared the antitumor effect of photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) as the photosensitizer, combined with cisplatin (CDDP) on AMC-HN3 human squamous cell carcinoma. AMC-HN3 cells were cultured and then incubated with various concentrations of CDDP and ALA. 632 nm diode laser was given at $6.0J/cm^2$ followed by incubation for 24 hours. The evaluation of cell viability was done by MTT assay. In vivo CDDP was injected intraperitoneally 24 hours prior to PDT. The anti-tumor effects of each treatment were measured by tumor volume change. Cell viability were 44.29% for the cisplatin-mediated chemotherapy group $(6.25{\mu}g/ml)$, 77.22% for ALA-PDT group, and 15.06% for the Combination therapy group. In vivo, the antitumor effect of photodynamic therapy was enhanced by combination of Cisplatin-mediated chemotherapy. Photodynamic therapy combined with administration of Cisplatin appears to enhance antitumor effect and to be a useful treatment modality.

• Biomedical Science Letters
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• v.17 no.3
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• pp.253-260
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• 2011

Chaga mushroom (Inonotus obliquus) extract has been known to have therapeutic effects, such as anti-inflammatory, hepato-protective, anti-oxidant and anti-tumor effect. In this study, we evaluated the effects of Chaga extract on the cytotoxic actions of cisplatin in HepG2 hepatoma cells. The viability of the HepG2 cells was decreased to 10% at 3 ${\mu}M$ cisplatin and to 20% at 500 ${\mu}g$/ml Chaga extract as measured by the MTT assay. The viability of HepG2 cells co-treated with cisplatin (3 ${\mu}M$) and Chaga extract (500 ${\mu}g$/ml) was decreased to 50% in compared with the control cells. The cytotoxicity of two drugs was revealed as apoptosis characterized by the chromatic condensation, nuclear fragmentation and the cleavage of pro caspase-3 in HepG2 cells. Also, the cells treated with combination of two drugs showed synergistically the loss of mitochondrial membrane potential and increase of intracellular ROS levels. Therefore, these results suggest that the combination treatment of cisplatin and Chaga extract induces apoptotic cell death in HepG2 cells and has more potential anti-tumor effect than cisplatin alone.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1581-1584
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• 2014

Background: The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. Materials and Methods: A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel ($75mg/m^2$, day 1) and cisplatin ($75mg/m^2$, day 1) was performed as a first line regimen every 21 days. Results: The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). Conclusion: The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3457-3461
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• 2015

Background: Previous studies have suggested that Morinda citrifolia (Noni) has potential to reduce cancer risk. Objective: The purpose of this study was to investigate the effect of Noni, cisplatin, and their combination on DNA repair genes in the SiHa cervical cancer cell line. Materials and Methods: SiHa cells were cultured and treated with 10% Noni, $10{\mu}g/dl$ cisplatin or their combination for 24 hours. Post culturing, the cells were pelleted, RNA extracted, and processed for investigating DNA repair genes by real time PCR. Results: The expression of nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and base excision repair gene XRCC1 was increased 4 fold, 8.9 fold, 4 fold, and 5.5 fold, respectively, on treatment with Noni as compared to untreated controls (p<0.05). In contrast, expression was found to be decreased 22 fold, 13 fold, 16 fold, and 23 fold on treatment with cisplatin (p<0.05). However, the combination of Noni and cisplatin led to an increase of 2 fold, 1.6 fold, 3 fold, 1.2 fold, respectively (p<0.05). Conclusions: Noni enhanced the expression of DNA repair genes by itself and in combination with cisplatin. However, high expression of DNA repair genes at mRNA level only signifies efficient DNA transcription of the above mentioned genes; further investigations are needed to evaluate the DNA repair protein expression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3907-3912
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• 2015

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

• YAKHAK HOEJI
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• v.47 no.3
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• pp.159-166
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• 2003

In order to study the clinical usefulness of crude polysaccharides fractionated from Eleutherococcus senticosus, EN-3, in eliminating tumors, we have investigated the effect of combination therapy on the murine tumor metastasis and growth models. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous (i.v.) administration of EN-3 (0.5, 5, and 50 $\mu\textrm{g}$/mouse) inhibited tumor metastasis compared with tumor control group in 33.6, 66.8, and 81.8％ respectively. The administration of EN-3 (50 $\mu\textrm{g}$/mouse) also exhibited a 66.1％ therapeutic effect on lung tumor metastasis. Although EN-3 induced no toxic effect on both tumor cell and normal splenocyte in the concentration below 100 $\mu\textrm{g}$/mι in in vitro, it induced significant proliferating activity on normal splenocyte in the concentration-dependent manner. In an analysis of NK-cell activity, i.v. administration of EN-3 (4∼100 $\mu\textrm{g}$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin (10 $\mu\textrm{g}$) and EN-3 (5 $\mu\textrm{g}$) induced synergistic effect on the inhibition of tumor metastasis in experimental tumor metastasis model produced by colon26-M3.1 cells. In addition, the combination treatments also exhibited prolongation of lifespan in S∼180 tumor bearing mouse for over the 60 days. Even though cisplatin (2.5 $\mu\textrm{g}$/mι) exhibited cytotoxicity to tumor cells and inhibited tumor growth over 95％ in in vitro, combination treatment with EN-3 (20 $\mu\textrm{g}$/mι) was induced splenocyte proliferation and produced cytokines, such as TNF-$\alpha$, IL-1 and IL-12, from the macrophages. These results suggested that EN-3 stimulate immune system non-specifically and apply to the biological response modifiers (BRM) in chemo-immunotherapy for tumor prevention.